Estimating the global burden of endemic canine rabies

Background: Rabies is a notoriously underreported and neglected disease of lowincome countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries.<p></p> Methodology/Principal Findings: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25- 159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%).<p></p> Conclusions/Significance: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.<p></p&gt

Polyclonal antibodies for the detection of Trypanosoma cruzi circulating antigens

Detection of Trypanosoma cruzi antigens in clinical samples is considered an important diagnostic tool for Chagas disease. The production and use of polyclonal antibodies may contribute to an increase in the sensitivity of immunodiagnosis of Chagas disease.Polyclonal antibodies were raised in alpacas, rabbits, and hens immunized with trypomastigote excreted-secreted antigen, membrane proteins, trypomastigote lysate antigen and recombinant 1F8 to produce polyclonal antibodies. Western blot analysis was performed to determine specificity of the developed antibodies. An antigen capture ELISA of circulating antigens in serum, plasma and urine samples was developed using IgY polyclonal antibodies against T. cruzi membrane antigens (capture antibody) and IgG from alpaca raised against TESA. A total of 33 serum, 23 plasma and 9 urine samples were analyzed using the developed test. Among serum samples, compared to serology, the antigen capture ELISA tested positive in 55% of samples. All plasma samples from serology positive subjects were positive in the antigen capture ELISA. All urine positive samples had corresponding plasma samples that were also positive when tested by the antigen capture ELISA.Polyclonal antibodies are useful for detection of circulating antigens in both the plasma and urine of infected individuals. Detection of antigens is direct evidence of the presence of the parasite, and could be a better surrogate of current infection status

Estimating the global burden of endemic canine rabies

Rabies is a fatal viral disease largely transmitted to humans from bites by infected animals —predominantly from domestic dogs. The disease is entirely preventable through prompt administration of post-exposure prophylaxis (PEP) to bite victims and can be controlled through mass vaccination of domestic dogs. Yet, rabies is still very prevalent in developing countries, affecting populations with limited access to health care. The disease is also grossly underreported in these areas because most victims die at home. This leads to insufficient prioritization of rabies prevention in public health agendas. To address this lack of information on the impacts of rabies, in this study, we compiled available data to provide a robust estimate of the health and economic implications of dog rabies globally. The most important impacts included: loss of human lives (approximately 59,000 annually) and productivity due to premature death from rabies, and costs of obtaining PEP once an exposure has occurred. The greatest risk of developing rabies fell upon the poorest regions of the world, where domestic dog vaccination is not widely implemented and access to PEP is most limited. A greater focus on mass dog vaccination could eliminate the disease at source, reducing the need for costly PEP and preventing the large and unnecessary burden of mortality on at-risk communities.S1 Text. Supporting bibliography.S1 Table. Estimates by country of rabies deaths, exposures, PEP use, prevented deaths, dog vaccination coverage, probability that a dog is rabid (RP), of bite victims receiving PEP (PP), DALYs, costs and 95% confidence intervals of estimates. Clusters to which countries are assigned are shown and inputs used for estimating parameters including the human development index and whetehr a country s rabies-free or endemic (RISK). Estimates of years of life lost (YLL) and DALYs (due to rabies and to adverse events from the use of nerve tissue vaccines) are shown under different assumptions (estimates under the assumption of no time discounting or age-weighting should be directly comparable to the 2010 Global Burden of Disease study).S1 Fig. Division of costs associated with rabies, prevention and control across sectors by cluster. Inset shows proportional expenditure in different clusters. Full details of countries by cluster are given in S1 Table. Asia 4 comprises: Philippines, Sri Lanka, Thailand (High PEP use); Asia 3 comprises Bhutan, Nepal, Bangladesh, Pakistan (Himalayan region); Asia 2 comprises Cambodia, Myanmar, Laos, Vietnam and Democratic People’s Republic of Korea; SADC comprises countries in the Southern African Development Community, Eurasia comprises Afghanistan, Kazakhstan, Kyrgyzstan, Mongolia, the Russian Federation, Turkmenistan, Tajikistan, and Uzbekistan.S1 Dataset. Model code and input data files including references, rationale and detail of Delphi process. The code folder contains seven R scripts: burden_model.R runs the model using data compiled in burden_1.R, after estimating parameters using: FitCovInc.R, FitPP.R, and creating Fig 2 (RabiesBurdenFig2.R). The script burden_results.R summarizes findings using the output of burden_model.R and burden_sensitivity.R runs the sensitivity analyses. The data folder contains 12 csv files called by the R code for the analyses, and one excel file (Vet. xlsx) with additional details about the data sources in vcountry2.csv and vcluster2.csv and with Delphi process estimates for dog vaccination coverage. Data sources are detailed in the relevant data sources and the details of the sources of data used in the analysis are in the supporting bibliography, S1 text.This study was funded by the UBS Optimus Foundation (http://www.ubs.com/optimusfoundation) and the Wellcome Trust (095787/Z/11/Z).http://www.plosntds.orgam201

El cerdo (Sus scrofa domesticus) como modelo experimental para la infección de Trypanosoma cruzi (mal de chagas)

Publicación a texto completo no autorizada por el autorEvalúa al cerdo doméstico como modelo experimental para la inoculación de Trypanosoma cruzi, en la búsqueda de una especie doméstica que signifique una alternativa más de modelo animal para diversos ensayos en esta enfermedad. Para este fin se inocularon a cuatro gorrinas de tres meses de edad, con una cepa de T. cruzi obtenida de cultivo celular, realizado en las instalaciones del Laboratorio de Investigación y Desarrollo. Utilizando las vías de inoculación sanguínea e intradérmica y utilizando dos diferentes dosis de inóculo: 1x10 6 y 5x10 6 tripomastigotes por animal, suspendidos en medio RPMI (Roswell Park Memorial Institute medium). Se colectaron muestras sanguíneas semanales para hacer pruebas directas (Microconcentración) e indirectas (EAE-ELISA y TESA Blot), por un periodo de cinco meses. Evaluándose a través de la prueba de microconcentración se obtuvo el 100% de animales positivos (4/4) desde el día 15 post-inoculación. Además se realizaron pruebas serológicas de TESA Blot (Blot con Antígeno excretorio-secretorio de tripomastigote), detectando IgG desde el día 20 post inoculación, resultando positivos el 100% de los animales (4/4). Para la prueba EAE- ELISA (ELISA con antígeno de extracto alcalino de epimastigote) se detectaron IgM desde el día 11 post-inoculación y detectando IgG desde el día 20 post-inoculación resultando positivos el 100% de los animales (4/4). Este estudio demostró la infección experimental en el cerdo, utilizando parásitos obtenidos por cultivo celular, a través de los métodos mencionados. La vía de inoculación intradérmica logró la infección al igual que la vía sanguínea. No se observaron signos clínicos de enfermedad.Tesi

Spatiotemporal analysis of canine rabies in El Salvador: Violence and poverty as social factors of canine rabies.

BACKGROUND:The incidence of canine rabies cases in El Salvador has decreased in the last decade since the establishment of intense control programs, such as massive vaccination campaigns implemented by the Ministry of Health. Socioeconomic crises in recent years have limited the access to certain areas across the country and have impacted surveillance and prevention campaigns, which places the country at risk for a resurgence of canine rabies.We aimedto describe the spatiotemporal patterns of canine rabies and its association with critical social factors in El Salvador from 2005 to 2014. METHOD:We included 459 cases of canine rabies. Several socioeconomic, demographic, and surveillance variables were modeled using a Poisson regression to evaluate their associations with the incidence of canine rabies. Spatial scan statistics were adjusted or unadjusted with covariates and applied to identify statistically significant clusters of canine rabies. Finally, a canine rabies risk map was created. RESULTS:A positive association and higher risk of canine rabies were found for low poverty zones, where it is suspected that urban slums contribute to ongoing rabies transmission (RR = 7.74). Violence had a negative association with rabies (RR = 0.663), which is likely due to reporting bias. Significant clusters were identified in all five epidemiological regions, and the Eastern region had the highest risk (RR = 50.62). The influences of the selected variables in cluster detection were confirmed by the adjusted analysis. Higher-risk townships were distributed from the Western to the Eastern regions of the country. CONCLUSION:Social factors are determinants of rabies in El Salvador and play a major role in national spatial patterns of the disease. There are high-risk areas for canine rabies across the country, and there were two persistent rabies foci during the study period. Examining the role of social factors can provide better insight into rabies in vulnerable countries, and socioeconomic factors can be key elements in developing better policies and interventions for rabies control

Results of the antigen capture ELISA compared to serology and qPCR.

<p>Results of the antigen capture ELISA compared to serology and qPCR.</p

Antigen capture ELISA in urine samples.

<p>Antigen capture ELISA in urine samples.</p

Animal immunization scheme.

<p>Animal immunization scheme.</p

SDS-PAGE of purified antibodies.

<p>A: Purified IgGs from alpaca; Lane 1 = IgG1, lane 2 = IgG2, lane 3 = IgG3, lane 4 = molecular weight marker. B: purified IgG from rabbits; lane 1 = IgG, lane 2 = molecular weight marker. C: purified IgY from eggs; Lane 1 = IgY, lane 2 = molecular weight marker. The arrows indicate the presence of IgG1 in the IgG2 purified fraction.</p